Nuclear magnetic resonance studies of phenylalanine analog interactions with normal and sicklen hemoglobin
Several phenylalanine derivatives have been found to inhibit the gelation of deoxygenated sickle hemoglobin (deoxy HbS). Proton and /sup 19/F-NMR techniques were used to monitor the interaction of selected phenylalanine derivatives with the Hb molecule by using fluorine containing phenylalanine derivatives, Hb labeled at the ..beta..93 position with N-(2,2,2-trifluoroethyl) iodoacetamide (IA-F/sub 3/), and by monitoring the relaxation rates of the C2 and C4 histidine protons. The results show that the /sup 19/F spin-spin relaxation times of L-phenylalanin-4-fluorobenzylamide (PheNBz1-F), which has a deoxy HbS antigelling activity comparable to that of the amino acid, tryptophan, are affected much more strongly by interaction with Hb than are those of glycin-4-fluorobenzylamide (GlyNBz1-F). In contrast, it is shown that N-(2,2,5,5-tetramethylpyrrolidin-1-oxy-3-carboxyl)-L-phenylalanine t-butyl ester (SL-Phe) exhibits specific binding to Hb, and an antigelling activity more than two orders of magnitude greater than that of phenylalanine. These results indicate that the fluorine nuclei strongly influenced by the presence of spin label nitroxide are located in a conformation within a few angstroms of the SL-Phe binding site. Proton NMR relaxation measurements of the C2 and C4 proton resonances from the ..beta..2, 4b143 and ..beta..146 histidine residues show significant and selective effects from the binding of SL-Phe to Hb, indicating that the SL-Phe binding site must be close to the side chains of these three residues. The strong antigelation activity of SL-Phe suggests that this binding site may be one of the intermolecular contact sites of importance to the deoxy HbS aggregation process.
- Research Organization:
- Illinois Univ., Chicago (USA)
- OSTI ID:
- 6985803
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEMOGLOBIN
CONFIGURATION INTERACTION
NUCLEAR MAGNETIC RESONANCE
PHENYLALANINE
FLUORINE 19
SICKLE CELL ANEMIA
SPIN-SPIN RELAXATION
STRUCTURAL CHEMICAL ANALYSIS
AMINO ACIDS
ANEMIAS
CARBOXYLIC ACIDS
DISEASES
FLUORINE ISOTOPES
GLOBIN
HEMIC DISEASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
RELAXATION
RESONANCE
STABLE ISOTOPES
SYMPTOMS
550201* - Biochemistry- Tracer Techniques